期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 14, 期 2, 页码 2601-2616出版社
MDPI AG
DOI: 10.3390/ijms14022601
关键词
electronegative LDL; HDL; cytokines; ceramide; diacylglycerol; lipoprotein aggregation; monocytes; phospholipase C
资金
- Spanish Society of Atherosclerosis SEA
- Ministry of Health ISCIII/FIS [PI09/0160, PI10/0265, CP04/0110, CP06/0220]
- La Caixa
Electronegative low-density lipoprotein (LDL(-)) is a minor modified LDL subfraction that is present in blood. LDL(-) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is counteracted by high-density lipoprotein (HDL). HDL also inhibits a phospholipase C-like activity (PLC-like) intrinsic to LDL(-). The aim of this work was to assess whether the inhibition of the PLC-like activity by HDL could decrease the content of ceramide (CER) and diacylglycerol (DAG) generated in LDL(-). This knowledge would allow us to establish a relationship between these compounds and the inflammatory activity of LDL(-). LDL(-) incubated at 37 degrees C for 20 h increased its PLC-like activity and, subsequently, the amount of CER and DAG. We found that incubating LDL(-) with HDL decreased both products in LDL(-). Native LDL was modified by lipolysis with PLC or by incubation with CER-enriched or DAG-enriched liposomes. The increase of CER in native LDL significantly increased cytokine release, whereas the enrichment in DAG did not show these inflammatory properties. These data point to CER, a resultant product of the PLC-like activity, as a major determinant of the inflammatory activity induced by LDL(-) in monocytes.
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